Over the last few years, the Zika virus pandemic brought into sharp focus our incomplete understanding and the fragility of the fetal development. Zika virus can lead to Congenital Zika Syndrome, which can cause serious congenital anomalies. Importantly, these congenital malformations are associated with significant and lifelong morbidity and increased risk of mortality. It is not clear how Zika virus is transmitted from mothers to the fetal brain and leads to these congenital malformations. However, an emerging body of evidence suggests Zika virus affects distinct human populations differently, and is associated with different outcomes in fraternal twins—one twin may be affected, while the other is developmentally typical.
Our overarching hypothesis is that different groups of people and/or distinct individuals have intrinsic genetic risk or protective factors. Using the Zika virus pandemic as a natural experiment, we propose a genome wide association study to identify population-specific, maternal and/or fetal risk or protective factors. To this end, we’ve established the Zika Genetics Consortium. Since Collaborating sites share a common protocol, phenotypic and genotypic data can be combined to confer more statistical power and help identify common variants with smaller effect size. Our hypothesis will be addressed in experiments of the following specific aims:
- To determine if common genetic variants with a large effect size are associated with microcephaly in Congenital Zika Syndrome; and
- To determine if rare variants in “target” or “Zika pathway” genes can contribute to microcephaly in Congenital Zika Syndrome.